Good news for the heart: The chronic use of rofecoxib causes adverse cardiovascular complications that prompted its withdrawal from the market. We recently modified rofecoxib into an NO-releasing, potent anti-inflammatory drug. Herein we describe the beneficial anti-hypertensive effects of the NO-releasing SO(2) NHOH COX-2 pharmacophore on blood pressure and its ability to enhance recovery in a cardiac ischemic reperfusion injury model.